Oregon Health & Science University
Glia are the primary immune responding cells in the brain and are thus highly attuned to changes in central nervous system (CNS) health. After any form of neural trauma, subsets of glia quickly respond by migrating to the site of damage and clearing degenerating tissue through phagocytic engulfment. This response contains the original insult and minimizes further damage to surrounding tissue. Unfortunately, the molecular mechanisms underlying these complex glial immune responses are poorly understood. Here, I provide the first direct evidence for the involvement of insulin-like signaling in the glial clearance response to acute CNS injury. Using a well established acute axotomy assay in
demonstrate that glial insulin-like signaling is critical for effective clearance of degenerating axonal debris in the adult brain. This effect is mediated through the insulin-like receptor (InR) and several downstream signaling components, all of which are highly conserved from Drosophila to humans. Additionally, I show that adult glial InR signaling is a positive regulator of the engulfment receptor Draper (Drosophila ortholog of mammalian MEGF10 and Jedi-1), a receptor that is highly upregulated in glia responding to CNS injury and plays an essential role in the glial clearance response. Furthermore, I demonstrate that forced expression of Draper in adult glia partially rescues the glial clearance defects caused by acute InR knockdown. Taken together, the work presented here demonstrates a novel yet critically important role for the insulin-like signaling pathway in innate glial immune responses. The insulin-like signaling pathway is a powerful regulator of transcription, translation, and metabolic homeostasis, and might represent a fundamental signaling mechanism used by glia to orchestrate the complex and varied cellular steps needed to achieve an effective glial clearance response to CNS damage.
Neuroscience Graduate Program
School of Medicine
Musashe, Derek Todd, "Insulin-like signaling regulates glial immune responses to axon degeneration in drosophila melanogaster" (2014). Scholar Archive. 3561.
Available for download on Tuesday, September 19, 2017